Mark Loeb

Probiotics for the Prevention of Clostridium difficile–Associated Diarrhea: A Systematic Review and Meta-analysis

66% (pooled relative risk, 0.34 [95% CI, 0.24 to 0.49]; I 2 0%). In a population with a 5% incidence of antibiotic-associated CDAD (median control group risk), probiotic prophylaxis would prevent 33 episodes (CI, 25 to 38 episodes) per 1000 persons. Of probiotictreated patients, 9.3% experienced adverse events, compared with 12.6% of control patients (relative risk, 0.82 [CI, 0.65 to 1.05]; I 2 17%). Limitations: In 13 trials, data on CDAD were missing for 5% to 45% of patients. The results were robust to worst-plausible assumptions regarding event rates in studies with missing outcome data. Conclusion: Moderate-quality evidence suggests that probiotic prophylaxis results in a large reduction in CDAD without an increase in clinically important adverse events.

Development of minimum criteria for the initiation of antibiotics in residents of long-term-care facilities: Results of a consensus conference

Establishing a clinical diagnosis of infection in residents of long-term-care facilities (LTCFs) is difficult. As a result, deciding when to initiate antibiotics can be particularly challenging. This article describes the establishment of minimum criteria for the initiation of antibiotics in residents of LTCFs. Experts in this area were invited to participate in a consensus conference. Using a modified delphi approach, a questionnaire and selected relevant articles were sent to participants who were asked to rank individual signs and symptoms with respect to their relative importance. Using the results of the weighting by participants, a modification of the nominal group process was used to achieve consensus. Criteria for initiating antibiotics for skin and soft-tissue infections, respiratory infections, urinary infections, and fever where the focus of infection is unknown were developed.

Surgical Mask vs N95 Respirator for Preventing Influenza Among Health Care Workers: A Randomized Trial

CONTEXT Data about the effectiveness of the surgical mask compared with the N95 respirator for protecting health care workers against influenza are sparse. Given the likelihood that N95 respirators will be in short supply during a pandemic and not available in many countries, knowing the effectiveness of the surgical mask is of public health importance. OBJECTIVE To compare the surgical mask with the N95 respirator in protecting health care workers against influenza. DESIGN, SETTING, AND PARTICIPANTS Noninferiority randomized controlled trial of 446 nurses in emergency departments, medical units, and pediatric units in 8 tertiary care Ontario hospitals. INTERVENTION Assignment to either a fit-tested N95 respirator or a surgical mask when providing care to patients with febrile respiratory illness during the 2008-2009 influenza season. MAIN OUTCOME MEASURES The primary outcome was laboratory-confirmed influenza measured by polymerase chain reaction or a 4-fold rise in hemagglutinin titers. Effectiveness of the surgical mask was assessed as noninferiority of the surgical mask compared with the N95 respirator. The criterion for noninferiority was met if the lower limit of the 95% confidence interval (CI) for the reduction in incidence (N95 respirator minus surgical group) was greater than -9%. RESULTS Between September 23, 2008, and December 8, 2008, 478 nurses were assessed for eligibility and 446 nurses were enrolled and randomly assigned the intervention; 225 were allocated to receive surgical masks and 221 to N95 respirators. Influenza infection occurred in 50 nurses (23.6%) in the surgical mask group and in 48 (22.9%) in the N95 respirator group (absolute risk difference, -0.73%; 95% CI, -8.8% to 7.3%; P = .86), the lower confidence limit being inside the noninferiority limit of -9%. CONCLUSION Among nurses in Ontario tertiary care hospitals, use of a surgical mask compared with an N95 respirator resulted in noninferior rates of laboratory-confirmed influenza. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00756574

Induction of Epitope-Specific Neutralizing Antibodies against West Nile Virus

ABSTRACT Previous studies have established that an epitope on the lateral ridge of domain III (DIII-lr) of West Nile virus (WNV) envelope (E) protein is recognized by strongly neutralizing type-specific antibodies. In contrast, an epitope against the fusion loop in domain II (DII-fl) is recognized by flavivirus cross-reactive antibodies with less neutralizing potential. Using gain- and loss-of-function E proteins and wild-type and variant WNV reporter virus particles, we evaluated the expression pattern and activity of antibodies against the DIII-lr and DII-fl epitopes in mouse and human serum after WNV infection. In mice, immunoglobulin M (IgM) antibodies to the DIII-lr epitope were detected at low levels at day 6 after infection. However, compared to IgG responses against other epitopes in DI and DII, which were readily detected at day 8, the development of IgG against DIII-lr epitope was delayed and did not appear consistently until day 15. This late time point is notable since almost all death after WNV infection in mice occurs by day 12. Nonetheless, at later time points, DIII-lr antibodies accumulated and comprised a significant fraction of the DIII-specific IgG response. In sera from infected humans, DIII-lr antibodies were detected at low levels and did not correlate with clinical outcome. In contrast, antibodies to the DII-fl were detected in all human serum samples and encompassed a significant percentage of the anti-E protein response. Our experiments suggest that the highly neutralizing DIII-lr IgG antibodies have little significant role in primary infection and that the antibody response of humans may be skewed toward the induction of cross-reactive, less-neutralizing antibodies.

Mupirocin-Resistant, Methicillin-Resistant Staphylococcus aureus Strains in Canadian Hospitals

ABSTRACT Mupirocin resistance in Staphylococcus aureus is increasingly being reported in many parts of the world. This study describes the epidemiology and laboratory characterization of mupirocin-resistant methicillin-resistant S. aureus (MRSA) strains in Canadian hospitals. Broth microdilution susceptibility testing of 4,980 MRSA isolates obtained between 1995 and 2004 from 32 Canadian hospitals was done in accordance with CLSI guidelines. The clinical and epidemiologic characteristics of strains with high-level mupirocin resistance (HLMupr) were compared with those of mupirocin-susceptible (Mups) strains. MRSA strains were characterized by pulsed-field gel electrophoresis (PFGE) and typing of the staphylococcal chromosomal cassette mec. PCR was done to detect the presence of the mupA gene. For strains with mupA, plasmid DNA was extracted and subjected to Southern blot hybridization. A total of 198 (4.0%) HLMupr MRSA isolates were identified. The proportion of MRSA strains with HLMupr increased from 1.6% in the first 5 years of surveillance (1995 to 1999) to 7.0% from 2000 to 2004 (P < 0.001). Patients with HLMupr MRSA strains were more likely to have been aboriginal (odds ratio [OR], 3.7; 95% confidence interval [CI], 1.5 to 9.4; P = 0.006), to have had community-associated MRSA (OR, 2.2; 95% CI, 1.0 to 5.0; P = 0.05), and to have been colonized with MRSA (OR, 1.7; 95% CI, 1.0 to 3.0; P = 0.04). HLMupr MRSA strains were also more likely to be resistant to fusidic acid (21% versus 4% for mupirocin-susceptible strains; P < 0.001). All HLMupr MRSA strains had a plasmid-associated mupA gene, most often associated with a 9-kb HindIII fragment. PFGE typing and analysis of the plasmid profiles indicate that both plasmid transmission and the clonal spread of HLMupr MRSA have occurred in Canadian hospitals. These results indicate that the incidence of HLMupr is increasing among Canadian strains of MRSA and that HLMupr MRSA is recovered from patients with distinct clinical and epidemiologic characteristics compared to the characteristics of patents with Mups MRSA strains.

Interferon-Mediated Immunopathological Events Are Associated with Atypical Innate and Adaptive Immune Responses in Patients with Severe Acute Respiratory Syndrome

ABSTRACT It is not understood how immune inflammation influences the pathogenesis of severe acute respiratory syndrome (SARS). One area of strong controversy is the role of interferon (IFN) responses in the natural history of SARS. The fact that the majority of SARS patients recover after relatively moderate illness suggests that the prevailing notion of deficient type I IFN-mediated immunity, with hypercytokinemia driving a poor clinical course, is oversimplified. We used proteomic and genomic technology to systematically analyze host innate and adaptive immune responses of 40 clinically well-described patients with SARS during discrete phases of illness from the onset of symptoms to discharge or a fatal outcome. A novel signature of high IFN-α, IFN-γ, and IFN-stimulated chemokine levels, plus robust antiviral IFN-stimulated gene (ISG) expression, accompanied early SARS sequelae. As acute illness progressed, SARS patients entered a crisis phase linked to oxygen saturation profiles. The majority of SARS patients resolved IFN responses at crisis and expressed adaptive immune genes. In contrast, patients with poor outcomes showed deviated ISG and immunoglobulin gene expression levels, persistent chemokine levels, and deficient anti-SARS spike antibody production. We contend that unregulated IFN responses during acute-phase SARS may culminate in a malfunction of the switch from innate immunity to adaptive immunity. The potential for the use of the gene signatures we describe in this study to better assess the immunopathology and clinical management of severe viral infections, such as SARS and avian influenza (H5N1), is therefore worth careful examination.

Use of Oseltamivir During Influenza Outbreaks in Ontario Nursing Homes, 1999–2000

To describe the experience of Ontario long‐term care facilities that used oseltamivir during influenza outbreaks in 1999/2000.

Antibiotic Use in Ontario Facilities That Provide Chronic Care

OBJECTIVE: To determine the incidence and variability of antibiotic use in facilities which provide chronic care and to determine how often clinical criteria for infection are met when antibiotics are prescribed in these facilities.DESIGN: A prospective, 12-month, observational cohort study.SETTING: Twenty-two facilities which provide chronic care in southwestern Ontario.PARTICIPANTS: Patients who were treated with systemic antibiotics over the study period.MEASUREMENTS: Characteristics of antibiotic prescriptions (name, dose, duration, and indication) and clinical features of randomly selected patients who were treated with antibiotics.RESULTS: A total of 9,373 courses of antibiotics were prescribed for 2,408 patients (66% of the patients in study facilities). The incidence of antibiotic prescriptions in the facilities ranged from 2.9 to 13.9 antibiotic courses per 1,000 patient-days. Thirty-six percent of antibiotics were prescribed for respiratory tract infections, 33% for urinary infections, and 13% for skin and soft tissue infections. Standardized surveillance definitions of infection were met in 49% of the 1,602 randomly selected patients who were prescribed antibiotics. Diagnostic criteria for respiratory, urinary, and skin infection were met in 58%, 28%, and 65% of prescriptions, respectively. One third of antibiotic prescriptions for a urinary indication were for asymptomatic bacteriuria. Adverse reactions were noted in 6% of prescriptions for respiratory and urinary infections and 4% of prescriptions for skin infection.CONCLUSIONS: Antibiotic use is frequent and highly variable amongst patients who receive chronic care. Reducing antibiotic prescriptions for asymptomatic bacteriuria represents an important way to optimize antibiotic use in this population.

Interventions to prevent aspiration pneumonia in older adults: a systematic review

A systematic review was conducted to assess the effectiveness of the following interventions for prevention of aspiration pneumonia (AP) in older adults: compensatory strategy/positioning changes, dietary interventions, pharmacologic therapies, oral hygiene, and tube feeding. Data sources included a key word search of the MEDLINE, EMBASE, Cochrane Library, CINAHL, and HealthSTAR databases and hand searches of six journals. Reference lists of relevant primary and review articles were searched. Studies included were randomized, controlled trials (RCTs) enrolling adults aged 65 and older at risk of and assessed for AP. Two investigators extracted data on population, intervention, outcomes, and methodological quality. Of the 17 identified RCTs, eight met the selection criteria, two addressed dietary management or compensatory swallowing, two assessed pharmacological therapies, one assessed oral hygiene, and three assessed tube feeding. None of the eight trials reported use of blinding, and allocation concealment was unclear in five. Use of amantadine prevented pneumonia in one trial of nursing home residents. The antithrombotic agent cilostazol prevented AP in another trial but resulted in excessive bleeding. Insufficient data exist to determine the effectiveness of positioning strategies, modified diets, oral hygiene, feeding tube placement, or delivery of food in preventing AP. Considering how common the problem of AP is in older adults, larger, high‐quality RCTs on the effectiveness of preventive interventions are warranted.

Modeling transmission of methicillin-resistant Staphylococcus aureus among patients admitted to a hospital.

OBJECTIVE To determine the impact of the screening test, nursing workload, handwashing rates, and dependence of handwashing on risk level of patient visit on methicillin-resistant Staphylococcus aureus (MRSA) transmission among hospitalized patients. SETTING General medical ward. METHODS Monte Carlo simulation was used to model MRSA transmission (median rate per 1,000 patient-days). Visits by healthcare workers (HCWs) to patients were simulated, and MRSA was assumed to be transmitted among patients via HCWs. RESULTS The transmission rate was reduced from 0.89 to 0.56 by the combination of increasing the sensitivity of the screening test from 80% to 99% and being able to report results in 1 day instead of 4 days. Reducing the patient-to-nurse ratio from 4.3 in the day and 6.8 at night to 3.8 and 5.7, respectively, reduced the number of nosocomial infections from 0.89 to 0.85; reducing the ratio to 1 and 1, respectively, further reduced the number of nosocomial infections to 0.32. Increases in handwashing rates by 0%, 10%, and 20% for high-risk visits yielded reductions in nosocomial infections similar to those yielded by increases in handwashing rates for all visits (0.89, 0.36, and 0.24, respectively). Screening all patients for MRSA at admission reduced the transmission rate to 0.81 per 1,000 patient-days from 1.37 if no patients were screened. CONCLUSION Within the ranges of parameters studied, the most effective strategies for reducing the rate of MRSA transmission were increasing the handwashing rates for visits involving contact with skin or bodily fluid and screening patients for MRSA at admission.